The overall goal of this proposal is to continue and expand the functions and capabilities of the Rat Resource and Research Center (RRRC) to provide biomedical investigators with the rat models, ES cells, related reagents and protocols they require for their research. In the last two years the biomedical community has developed several technologies to make targeted mutations (e.g., knock-outs and knock-ins) in rats. As a result the number of genetically engineered rat models and the number of investigators using rat models for biomedical research is likely to increase dramatically. The RRRC provides a unique repository service to the biomedical community for importing, storing and distributing a vast number of rat strains; as well as performing research that improves the function of the Resource Center. In addition to the animal repository, cryostorage, and distribution functions, the RRRC proposes to expand its function to assist investigators in the use of new rat gene targeting technologies and the unique challenges associated with these. The RRRC will do this by providing protocols for targeting and ES cell culture along with technical training in rat gene targeting. By expanding our services, the RRRC will serve as a much-needed resource for biomedical research investigators using rats in biomedical research.